It has been demonstrated that CD8-positive CTLs recognize epitope peptides derived from tumor-associated antigens (TAAs) on the major histocompatibility complex (MHC) class 1 molecule, and then kill the tumor cells. Since the discovery of melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPLs 1, 2), and some of these TAAs are now in the process of clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for the proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development and thus clinical application of peptide vaccination strategies for various types of cancer is ongoing (NPLs 3 to 10). To date, several clinical trials using these TAA derived peptides have been reported. Unfortunately, many of the current cancer vaccine trials have shown only a low objective response rate (NPLs 11 to 13). Accordingly, there remains a need for new TAAs as immunotherapeutic targets.
The WDHD1 gene (GenBank Accession No: NM—007086 or NM—001008396), composed of the WD repeat and the high-mobility group box DNA binding protein 1, has been identified by genome-wide gene expression profile analyses as a gene that is over-expressed in a large proportion of lung and esophageal carcinomas. In addition, WDHD1 likely plays an important role in lung and esophageal carcinogenesis as a cell cycle regulator and as a downstream molecule in the phosphoinositide 3-kinase/AKT pathway (NPL 14). Taken together, this data suggests that WDHD1 may be a suitable target for cancer immunotherapy, particularly lung and esophageal cancer immunotherapy.